Effect of consumption of catechin-rich green tea on pharmacokinetics of simvastatin in healthy volunteers

Background and purpose: Green tea has been reported to have various health benefits including cancer prevention and antiox- idative effect. Catechins, the main flavonoids in green tea, are considered to be potential components of these effects. Recently, a case report suggested that the consumption of catechin-rich green tea is associated with simvastatin intolerance. The present study aimed to evaluate the effect of catechin-rich green tea consumption on the pharmacokinetics of simvastatin lactone (SIM) and simvas- tatin acid (SVA), which are a prodrug and an active metabolite of simvastatin, respectively. Methods: In an open-label, two-way crossover study with 14 days washout, a single oral dose of 10mg SIM was administered to 12 healthy Japanese male volunteers (23–26 years old; body weight, 65.1±2.4 kg) after drinking of green tea (700mL/day, total catechinsof1080mg)orwater for2weeks. Bloodsampleswerecol- lected up to 24h after the administration. Plasma concentrations of SIM and SVA were determined using LC/MS/MS. Pharmacokinetic parameters were estimated by noncompartmental analysis. Results and discussion: Chronic consumption of catechin- rich green tea led to increases in the area under the plasma concentration-time curve (AUC0–∞) andmaximum concentration (Cmax) of SIM by 1.6- and 1.3-folds, respectively, as compared to water. No change was observed in the elimination half-life of SIM between green tea andwater, indicating that catechinsmainlymay inhibit SIMmetabolism in the intestine. In addition, green tea con- sumption significantly increased AUC0–∞ and Cmax of SVA by 1.5 and 1.6-folds, respectively, suggesting that green teamay affect not only the pharmacokinetics, but also the pharmacodynamics of SVA. Conclusion: The chronic consumption of catechin-rich green tea may cause the clinically relevant interaction with simvastatin.